title: De novo generation of an axially vascularized processed bovine cancellous-bone substitute in the sheep arteriovenous-loop model.
abstract: OBJECTIVE
  The aim of this study was to generate an axially vascularized bone substitute. The arteriovenous (AV)-loop approach in a large-animal model was applied in order to induce axial vascularization in a clinically approved processed bovine cancellous bone (PBCB) matrix of significant volume with primary mechanical stability and to assess the course of increasing axial vascularization.
  
  
  METHODS
  PBCB constructs were implanted into 13 merino sheep together with a microsurgically created AV loop in an isolation chamber. The vascularization process was monitored by sequential magnetic resonance imaging (MRI) scans. Explants were subjected to micro-computed tomography (micro-CT) analysis, histomorphometry and immunohistochemistry for CD31 and CD45.
  
  
  RESULTS
  Increasing axial vascularization in PBCB constructs was quantified by histomorphometry and visualized by micro-CT scans. Intravital sequential MRI scans demonstrated a significant progressive increase in perfused volume within the matrices. Immunohistochemistry confirmed endothelial lining of newly formed vessels.
  
  
  CONCLUSIONS
  This study demonstrates successful axial vascularization of a clinically approved, mechanically stable bone substitute with a significant volume by a microsurgical AV loop in a large-animal model. Thus microsurgical transplantation of a tissue-engineered, axially vascularized and mechanically stable bone substitute with clinically relevant dimensions may become clinically feasible in the future.
authors.affiliation: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Erlangen, Germany. Justus.beier@uk-erlangen.de
authors.forename: J P
authors.initials: JP
authors.lastname: Beier
authors.forename: A
authors.initials: A
authors.lastname: Hess
authors.forename: J
authors.initials: J
authors.lastname: Loew
authors.forename: J
authors.initials: J
authors.lastname: Heinrich
authors.forename: A M
authors.initials: AM
authors.lastname: Boos
authors.forename: A
authors.initials: A
authors.lastname: Arkudas
authors.forename: E
authors.initials: E
authors.lastname: Polykandriotis
authors.forename: O
authors.initials: O
authors.lastname: Bleiziffer
authors.forename: R E
authors.initials: RE
authors.lastname: Horch
authors.forename: U
authors.initials: U
authors.lastname: Kneser
mesh_terms: D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001857:Bone Matrix / Q000098:blood supply; D018786:Bone Substitutes; D016025:Bone Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000098:blood supply* / Q000000981:diagnostic imaging; D002417:Cattle; D005260:Female; D021621:Imaging, Three-Dimensional; D018810:Magnetic Resonance Angiography; D023421:Models, Animal; D012756:Sheep; D012826:Silicone Elastomers; D023822:Tissue Engineering; D055114:X-Ray Microtomography
chemical_list: D018786:Bone Substitutes; D012826:Silicone Elastomers